Labeling patterns of ALA by succinate or glucose via the TCA cycle or glutamine. (A) The TCA cycle is shown with the carbons of intermediate compounds color coded to their original source. Carbons coming from glucose via acetyl-CoA are black. These carbons become the 2 carbons distal to the amino group of ALA. Carbons from exogenously provided succinate that transit the TCA cycle once are colored red and become the 2 carbons adjacent to the glycine-derived (green) carbon and amino group of ALA. Succinate that is directly converted to succinyl-CoA by the ATP-dependent SCS reverse reaction is colored yellow. All 4 succinate carbons that enter in this fashion are incorporated into ALA. Glutamine carbons are labeled in blue. Following decarboxylation to α-KG, all 4 atoms are incorporated into ALA. If these carbons were to pass through the TCA cycle, they would label ALA as is shown in red for succinate. (B-C) Ball and stick models of protoporphyrin heme IX are shown. In both panels, carbon atoms originating from glycine are in green. (B) Carbons originating from glucose via the TCA cycle as shown in panel A are black. Because of decarboxylations during porphyrin synthesis, only 10 glucose-derived carbons can contribute to the final heme, whereas up to 16 carbons from succinate molecules that transits the cycle (red) could potentially end up in heme. (C) Carbons originating from glutamine are in blue. It should be noted that if succinate is directly converted to succinyl-CoA by the ATP-driven reverse SCS reaction, then its labeling pattern would be identical to what is shown for the glutamine-derived carbons.